Phospholipids (PL) are converted into lipid biomarkers by the action of phospholipases and reactive oxygen species (ROS), which are activated or released under certain physiological and pathophysiological conditions. Therefore, the in vivo concentration of such lipid biomarkers [e.g., lysophospholipids (LPLs)] is altered in humans and animals under different conditions such as inflammation, stress, medication, and nutrition. LPLs are particularly interesting because they are known to possess pro- and anti-inflammatory properties and may be generated by two different pathways: either by the influence of phospholipase A₂ or by different reactive oxygen species that are generated in significant amounts under inflammatory conditions. Both lead to the cleavage of unsaturated acyl residues. This review provides a short summary of the mechanisms by which lipid biomarkers are generated under in vitro and in vivo conditions. The focus will be on lysophosphatidylcholine (LPC) because usually, this is the LPL species which occurs in the highest concentration and is, thus, easily detectable by chromatographic and spectroscopic methods. Finally, the effects of lipid biomarkers as signaling molecules and their roles in different human and animal pathologies such as infertility, cancer, atherosclerosis, and aging will be shortly discussed.

Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mt^FVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4⁺ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.

Lipids are involved in a broad spectrum of canonical biological functions, from energy supply and storage by triacylglycerols to membrane formation by sphingolipids, phospholipids and glycolipids. Because of this wide range of functions, there is an overlap between age-associated processes and lipid pathways. Lipidome analysis revealed age-related changes in the lipid composition of various tissues in mice and humans, which were also influenced by diet and gender. Some changes in the lipid profile can be linked to the onset of age-related neurodegenerative diseases like Alzheimer’s disease. Furthermore, the excessive accumulation of lipid storage organelles, lipid droplets, has significant implications for the development of inflammaging and non-communicable age-related diseases. Dietary interventions such as caloric restriction, time-restrictive eating, and lipid supplementation have been shown to improve pertinent health metrics or even extend life span and thus modulate aging processes.

Legionella pneumophila is the primary causative agent of Legionnaires’ disease. The mutant-type strain interrupted in the ORF7 gene region responsible for the lipopolysaccharide biosynthesis of the L. pneumophila strain Heysham-1, lacking the O-acetyl groups attached to the rhamnose of the core part, showed a higher surface polarity compared with the wild-type strain. The measurement of excitation energy transfer between fluorophores located on the surface of bacteria and eukaryotic cells showed that, at an early stage of interaction with host cells, the mutant exhibited weaker interactions with Acanthamoeba castellanii cells and THP-1-derived macrophages. The mutant displayed reduced adherence to macrophages but enhanced adherence to A. castellanii, suggesting that the O-acetyl group of the LPS core region plays a crucial role in facilitating interaction with macrophages. The lack of core rhamnose O-acetyl groups made it easier for the bacteria to multiply in amoebae and macrophages. The mutant induced TNF-α production more strongly compared with the wild-type strain. The mutant synthesized twice as many ceramides Cer(t34:0) and Cer(t38:0) than the wild-type strain. The study showed that the internal sugars of the LPS core region of L. pneumophila sg 1 can interact with eukaryotic cell surface receptors and mediate in contacting and attaching bacteria to host cells as well as modulating the immune response to infection.